Key regulatory decisions for big pharma in the second half

After receiving a setback earlier in the year from US regulators over its key long-acting insulin products, Novo Nordisk was today served up a second helping of disappointment. The FDA has decided to bypass the October approval date for Tresiba and Ryzodeg and instead ordered an advisory panel for the two drugs in November. The US green light for the two products had been slated as one of the key product approvals in the second half of the year, so with authorisation now looking more likely in early 2013 Novo will have to do without the second and fourth biggest growth drivers in its pipeline for a bit longer.

While Novo may be nursing its disappointment there are still a number of big pharma companies waiting to hear the fate of some of their most promising late-stage drugs. Roche is facing two key European decisions, including Avastin in ovarian cancer and Perjeta in breast cancer. The battle of the blood thinners also moves from the US to Europe with Eliquis and Xarelto slugging it out for approvals in a range of indications. Other regulatory results that will be keenly watched include European and US nods for Gilead’s Quad, and US approval for Pfizer’s JAK-3 inhibitor tofacitinib, which would make it the first drug of its kind in rheumatoid arthritis (see table).

Regulatory decisions

Product

Company

Pharmacological class

Event

Indication

Date

Product NPV ($bn)

NPV as % of Market Cap

Avastin

Roche

Anti-VEGF MAb

EU approval

Ovarian cancer

Q3

27.5

18%

Perjeta

Roche

Anti-HER2 (ErbB-2) MAb

EU approval

Breast cancer

Q3

8.9

6%

Xarelto

Bayer

Factor Xa inhibitor

EU approvals

ACS, PE and DVT

Q3, Q4

7.8

13%

Eliquis

Bristol-Myers Squibb

Factor Xa inhibitor

EU approval

Stroke prevention

Q3

7.0

12%

Afinitor

Novartis

Rapamycin analogue (mTOR inhibitor)

US approval

Breast cancer

Q3

6.9

7%

Lucentis

Roche

Anti-VEGF Mab

Ad Com, US approval

DME

26 Jul, Q3

5.4

4%

Eliquis

Pfizer

Factor Xa inhibitor

EU approval

Stroke prevention

Q3

4.8

3%

Quad

Gilead Sciences

NRTI, HIV integrase inhibitor & CYP3A inhibitor

EU and US approval

HIV-1

Q3

4.3

11%

Tofacitinib

Pfizer

JAK-3 inhibitor

US approval

RA

Q3

4.0

2%

Erbitux

Merck KGaA

Anti-EGFr MAb

EU approval

NSCLC

Q3

3.4

15%

Tresiba

Novo Nordisk

Insulin

Ad Com

Diabetes

Nov 8

3.0

5%

Ryzodeg

Novo Nordisk

Insulin

Ad Com

Diabetes

Nov 8

2.6

4%

Bexsero

Novartis

Meningococcal B vaccine

EU approval

Meningitis B

Q3

2.8

2%

Abraxane

Celgene

Taxane

US approval

NSCLC

Q4

1.9

7%

Aubagio

Sanofi

PDGF tyrosine kinase & DHODH inhibitor

US approval

MS

Q3

0.9

1%

Eylea

Bayer

VEGFr kinase inhibitor

EU and US approval

Wet AMD (EU), CRVO (US)

Q3, Sep 23

0.8

1%

Omontys

Takeda

Erythropoietin stimulator

EU approval

Anemia

Q4

0.6

2%

Lyxumia

Sanofi

GLP-1 agonist

EU approval

Diabetes

Q4

0.6

1%

Zaltrap

Sanofi

VEGFr kinase inhibitor

EU and US approval

Colorectal cancer

Q3

0.4

0%

Novo will no doubt be cursing the decision by the FDA to stymie its plans again to launch degludec. Approval of the drug had already been put back by three months to October after the review period was extended. With this latest delay, the group will have to wait to wrestle some of the long-acting insulin market from Sanofi, as well as to mount a defence against generic competition in its core insulin market.

While Novo may be suffering at the hands of the regulator, many are expecting a much easier time for Pfizer’s tofacitinib. With the backing of an FDA panel already behind it, the drug stands a very good chance of becoming the second janus kinase approved, after Jakafi (Pfizer’s JAK inhibitor gets backing for broad RA label, May 10, 2012).

Mystery still surrounds what RA population the drug will be used in, but many believe that whatever its label the drug is still likely to be prescribed after incumbents Humira and Enbrel as its longer-term safety profile is assessed in the real world. Even though there are concerns over lymphomas, this potential second-line use is forecast to generate blockbuster sales. Consensus forecasts for 2018 put sales at $1.88bn.

Making up lost ground

Following the huge pipeline disappointment in the form of dalcetrapib's failure, the second half of 2012 will be an important one for Roche, which needs to make up some ground. Getting two cancer treatments approved in Europe will almost certainly help.

Perjeta (pertuzumab), already ready approved in the US to treat patients with HER2-positive metastatic breast cancer, is widely expected to win marketing consent in Europe given the limited options for patients at this stage of their disease. The addition of this new geography should help the drug achieve the $2.48bn of sales by 2018 that are currently forecast (Roche scores big breast cancer win as more pivotal data approach, June 11, 2012).

Roche is also looking to extend the reach of the already mighty Avastin with EU authorisation in ovarian cancer for women who have relapsed after chemotherapy. Impressive results revealed at Asco show that the drug improved median progression free survival from 3.4 months to 6.7 months; there was also a strong trend towards overall survival data from the data presented. If overall survival is confirmed it will represent a significant treatment leap for this very sick set of patients.

Although Gilead appears to be all about its hepatitis C pipeline these days, the group’s core HIV franchise should not be forgotten and approval of Quad in the US and Europe this autumn could serve as a welcome aide-memoire. The drug, which will use only Gilead produced products, is set to generate sales of $2.79bn by 2018 and will be the second biggest growth driver over the next six years, behind GS-7977.

While Quad has not demonstrated superior efficacy to current best-seller Atripla, it does have reduced central nervous system side effects which should ensure its move to blockbuster status, assuming the FDA does not pull the drug up on its effects on kidney function (Positive Quad vote protects Gilead's HIV franchise, May 14, 2012).

Second bite at the cherry

One drug regulators on both sides of the water have given the red card to is Erbitux in non-small cell lung cancer as a first line treatment. Development partners Eli Lilly and Bristol-Myers Squibb have already given up on trying to secure US approval, but Merck KGaA took the decision last year to soldier on in Europe. Merck has, however, chosen to narrow its focus to patients with high EGFR expression. The decision due any time now will determine if this strategy pays off.

Having failed to win approvals in key indications in the US, both Eliquis and Xarelto are scheduled to have second bites at the cherry in Europe this quarter. First up is Xarelto, which is due to hear from the regulator at the end of this week about secondary prevention after acute coronary syndrome. In June the group received a complete response letter from the FDA in this indication, while approval in this indication is not vital for Xarelto’s future success it would have been a way of differentiating it from Eliquis.

For Eliquis getting approval in stroke prevention could make up for the shock of the drug receiving a complete response letter in the US in June, an event that came out of the blue for many observers. As Bristol-Myers Squibbs biggest growth driver and one of the drugs Pfizer is hoping will help fill the yawning chasm left by Lipitor, getting its first approval will go a long way to helping sentiment as they try to fulfil data requests from the FDA.